Although it is known that cytokines trigger rapid tyrosine phosphorylation of a common set of cellular proteins as well as induction of several of the same early response genes, the mechanisms by which these genes are activated is not well understood. We have previously shown that the interferons, IL-6, LIF and OSM stimulate the assembly of protein complexes which recognize conserved sequences within the enhancers of two genes (IRF-1 and FcgRI) that are rapidly activated by these cytokines. These enhancers are known to be required for transcriptional induction of these genes by IFNg. Assembly of the DNA-binding protein complexes occurs within minutes after ligand addition and depends upon tyrosine phosphorylation. These complexes contain the p91 transcription factor, which is tyrosine phosphorylated in response to these cytokines. Thus, many cytokines activate p91 and, this supports the concept that sets of tyrosine phosphorylated proteins may be responsible for the cytokine regulated expression of early response genes. In contrast, immune complexes (IC) modulated the immune response in part by their ability to inhibit interferong (IFNg) dependent gene expression. We examined the mechanisms by which IC suppress IFNg induced expression of the Fcg receptor I gene (Fcgr1) in human monocytes, and found that culture of human monocytes on IC inhibits IFNg induced expression of the Fcgr1 gene by preventing tyrosine phosphorylation of p91, thereby inhibiting the formation of the GRR binding complex, FcRFg. We have gone on to show that whereas IC inhibits IFNg-induced gene expression, components of the extracellular matrix (ECM) are capable of enhancing the IFN-induced expression of the FcgRI gene. The mechanism whereby FcgRI expression was enhanced in this model system was explored. We have found that exposure of monocytes to cell-binding components of fibronectin for as little as 15 minutes was sufficient to enhance the IFN-induced expression of FcgRI gene by 10 fold. Similarly, there was a concomitant increase in the level of phosphorylation of the kinases JAK1, JAK2, and p91, suggesting that the mechanism whereby the ECM enhances the IFN-induced response is through the directed stimulation of the IFN signalling pathway which is comprised of JAK1, JAK2 and p91.